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Investigational Agent EDG-5506 Shows Promising 2-Year Data in Becker Muscular Dystrophy
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After 2 years of treatment, EDG-5506, otherwise known as sevasemten, was well-tolerated, with rapid and sustained decreases in biomarkers of muscle damage.
Joanne Donovan, MD, PhD
At the 2024 American Academy of Neurology (AAN) Annual Meeting, held April 13-18, in Denver, Colorado, Edgewise Therapeutics presented new 2-year data from the pivotal ARCH open-label trial (NCT05160415) assessing its investigational agent EDG-5506 in adults with Becker muscular dystrophy. All told, the therapy was well tolerated at all doses, demonstrated rapid and sustained decreases in multiple biomarkers of muscle damage, and stabilized functional assessments with trends toward improvement.
Becker, a severe condition that leads to progressive loss of motor function, has currently no approved therapies for the condition. ARCH, an open-label, single-center study, included 12 ambulatory males aged 18 to 55 years with a dystrophin mutation and a Becker phenotype, not on corticosteroids, who were followed for 24 months. At the conclusion of the 24-month period, investigators observed a –0.2 mean change in North Star Ambulatory Assessment (NSAA), which significantly diverged from a natural history average change of –2.4.
"We are pleased by the promising and consistent functional results observed over two years of treatment with sevasemten, together with the favorable safety and tolerability profile," Joanne Donovan, MD, PhD, chief medical officer at Edgewise, said in a statement.1 "We thank the Becker community for engaging with us on this promising therapy."
After 2 years of treatment, EDG-5506, otherwise known as sevasemten, was well-tolerated, with no dose reductions or adjustments made. Of the recorded adverse events (AEs), COVID-19 (n = 5), fall (n = 4), dizziness (n = 4), and arthralgia (n =4) were the most common observed. In addition, there were no treatment discontinuations because of AEs, as well as no serious AEs recorded. Overall, there were 3 withdrawals, 2 of whom are planning to enroll in separate open-label extensions.
Throughout the 24-month period, investigators observed rapid and sustained decreases of relevant biomarkers of muscle damage, including creatine kinase, fast skeletal muscle troponin I, and myoglobin. In addition, over that time, there was no significant change in hand grip strength or measures of endurance, explained through 100-Meter Timed Test Velocity and Maximum Grip Strength. Edgewise concluded that the positive 2-year data further support the hypothesis that a reduction in contraction-induced muscle damage in muscle dystrophies has the potential to preserve function and halt disease progression in Becker.
Barry Byrne, MD, PhD
EDG-5506, an orally administered small molecule agent, is designed to selectively limit the exaggerated muscle damage caused by the absence or loss of functional dystrophin. The therapy is anticipated to be used as a single agent treatment, but may also provide a synergistic or additive effect in combination with available therapies or therapies currently in development.
"Becker is a devastating neuromuscular disease that currently has no treatment,” Barry Byrne, MD, PhD, director of the Powell Gene Therapy Center at the University of Florida and chief medical advisory of the Muscular Dystrophy Association (MDA), said in a statement.1
"Once symptoms of muscle weakness occur, individuals with Becker have a relentless course of disease progression. In my experience, each one-point decrease in NSAA represents a loss of function important to daily activities. I have been closely following the progress of sevasemten in the clinic and am encouraged by the two-year results and the potential of this novel muscle-targeted therapy for individuals with Becker."
EDG-5506 is currently being evaluated in several other studies, including the ongoing Grand Canyon trial (NCT05290191), which is anticipated to enroll 120 adult males with Becker in the US and Europe. The study, an 18-month trial further assessing efficacy and safety of the agent, includes ambulatory patients with a mutation in the DMD gene with Becker phenotype who have an NSAA score between 5-32. Grand Canyon will last a total of up to 20 months, with a screening period of up to 4 weeks and a 4-week follow-up period after the 18-month treatment period.
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